Haloarylhydroxyalkyl-ureas



l l l Patented Dec. 22, 1953 2,563,729,; HAnoAnEHYoReXY amm-mms Dela are.

No Drawing. m plicafiomnmemueee Sl'eriahNo. 318,728.;

7 Claims. 31 Thi inv n en re a s toe new. la sei or an ni rog n compp.und nart l lx, t re.- Iat'esto'a new classof ie-su sti uted.' eaeandito heir pr par ion This. pplication. is a, continuationm art of our. conending application" Serial; Na, 18. 531 ledlsentember 2.1; 1950)., now. abandonedi the; sizable. number of: relatively! hi h 110: Ieicular, weight trifesubstitutecl urea s; containing enaromatieerounwh ch have, been exn iored;,,few possess satisfaetory water; solubility, required; for maxfnmm emcieney, in certain applications, papicu arm tho -401a b lo ical ature.

It. is, an; object, of this invention to proyi'de a new class of"tri-substitutecfureas and a method fortheir preparation, A fku-rther abject is taprovide a neveclass of li iil-fi bstitnteiureas which possess appreciable water soIubility. Another object is to provide new: trr-substituted ureas useful chemical intermediates-and infherbicidal compositions. Qtherg obj efets will appear hereinafter.

The objects of this inventi'on' are" accomplished by providing" thenew class f'*N;N",N -l3li-S1ibSfiftutedfureas having a hydrogenatom directly attached to one of the urea nitrogen atoms,- N, which is bond'edfto a nuclear carbon of-a halogenoargl radical; theother urea nitrogen atom, N; being disubstitutedi and joined to one to two hydroxyalkyl ra'olicajls, any other N substituent beinganalkyr radical}; preferablyof" one tofonr carbon atoms; This new cl'ass or? ureas-is-representefibytheformula:-

wherein It iszahalogenqar l radfcah, R is a droxyalkyl radical, and Rf represent hydroxyalkyl or alkyl radicals; When R" is hydroxs ells is la s o ureas an sieneteda i.- (halogenoaryD' L1, b.i' j(hdl'QXyaky1)urea and when aryl is phenyl; this class can be designated as: 3' (halogenophenyli'b -'s 11,]; bis-s: (hydroxyalkyll ureas.

N;N ,N"tri-substitutecf ureas: having onesuhstituent, an aromatic radical; 011 one ofJ-the urea mitrogem atoms and at least one hydroxylated I genoarniisocyane e BfiQ R bein a Hakeem:

alkylradical on the disubst'rtut'ed other urea nitrogen; have" been found to be: versatile chemtcal-intermediatesWhiohpossessappreciablewater solubility-and activity inv herbicidal'z'compositions.

A convenient method for preparing the new ureasof this invention is illustratedby the tel lowing general equation 61*) which the haloi-i me ical s acted s all n hem call equiv len amo n s.

eminent he tor-melee V Rf wh neiegfi' amen the-.s memeeemez tee v y design ted er t.,,ese s mbe si the formula of the new, ureas or; the invention:

o) R o R or? he nrena etiqer Q f 3am:

Anhouehrthe above bi un ional seeon emelt- Qhatie. am nes sus ptible. o; chemical" fi on-at eamina andl r. h dm ernn sb tz been found that by the procedure he ein e: scribed selective reaction with the amino groups can be accomplished with relative ease and in seed; a leles A u t-table eme siure. consists. n dropwise addition with stirring at a temperature o-ffrpnrfl to 1100 6. or the halogenoaryl isocyanateto tl' e secorrdary amine; d-issolved -or suspended? in an inert li'quici; medium; for example, dioxane, benzene; etc:, and continuing the-react with stfrring' untircompleted: "macawo pel s, lner ec e d m; eeh' pave o sefcon'daryaliphaticamine-wilTordinerilybesatisfactora. a d? al ough no e sa 2 59 erabie tq. se essent l r ead-mu in' d e conducting the'reaction;

The. ati ofisoerana e m ne c n e rie widely, but for most satisfactory resgltsj: it' is preferred to use the secondary amine in amom excess of to ov er tl eaisoeyanate employed. heh st ar gen ra b i ed a ga temperature in the range ofto Under the; roregumaconditions; the n aetiere.

with; a/ sec n ary,- alienate- 3 is complete in a relatively short time, usually two hours or less, after the reactants have been thoroughly mixed at the specified temperature.

The urea obtained can be isolated by crystallization, extraction, or other suitable means, depending to a large extent on whether the urea is a solid or a liquid and the nature of the reaction media employed. For example, when dioxane or other inert water-soluble reaction medium is employed, solid ureas of a satisfactory degree of purity can usually be isolated by dilutting the reaction mixture with benzene, ethylene dichloride or other similar solvent, and removing the precipitated urea by filtration. If necessary, further purification can be achieved through crystallization, in most instances from dioxane or benzene, or a mixture of these solvents.

The halogenoaryl isocyanates used as starting materials can be prepared by the general method described in the literature EVittenet, Bull. Soc. ,Chim. [3] 21, 586, 954 (1899) Organic Syntheses, Collective, vol. II, page 453; and U. S. Patent 2,428,843] which consists in heating the halogenoaryl carbamyl chloride first obtained by treating the halogenoaryl primary amine with phosgene at ordinary temperature in the presence of an appropriate solvent or reaction media.

The invention is illustrated in greater detail by the following examples in which parts, un-

less otherwise specified, are by weight:

EXAMPLE I 3-(p-chlorophenyl) -1 ,1 -bz's (Z-hydroxyethyl) area To a stirred solution of 15.3 parts of p-chlorophenyl isocyanate in 160 parts of benzene, was added rapidly at 15 C., 12.6 parts of diethanolamine. The reaction temperature was maintained at 15-l8 C. for 4 minutes by external cooling and then permitted to rise to 25 C. over a period of 1.1 hours. The reaction was further heated to reflux (80 C.) for 15 minutes. An insoluble oil separated from which the benzene was removed by decantation. Upon standing at room temperature for several hours, the oil crystallized into stout prisms which were slurried with 150 parts of cold water to remove excess diethanolamine, filtered, and washed with cold water. After drying in a vacuum desiccator over phosphoric anhydride, 22.4 parts of shiny r white crystals melting at 88-891 C. was obtained. The yield of 3-(p-ch1orophenyl) -1,1- bis(2-hydroxyethyl) urea was 87% of theoretical. AnaL-Calcd for C11H15C1N2O3! Cl, 13.75%.

Found: C1, 13.72%, l .3.66%.

EXAMPLE II 3- (p-bromophenyl) -1 ,1 -bis (Z-hydromyethyl) urea The resulting white precipitate was filtered and .air dried. .There was thus obtained 61 parts (84% of the theoretical yield) of B-(p-bromophenyl)-1,1-bis(2-hydroxyethyl) urea melting at AnalQ-Calcd for Ciel-lisBrNzo: Br, 26.4%. Found: Br, 26.8%.

EXAMPLE III 1 3- (p-iodophenyl) -1,1-bis(2-hydro.ryethyl) urea --A solution of 61.5 parts of p-iodophenyl isoteam cyanate in 103 parts of dry dioxane was added dropwise to a stirred solution of 29 parts of diethanolamine in 206 parts of dry dioxane. There was an immediate liberation of heat. The rate of addition was controlled so that the temperature did not rise above about 35 C. When the addition was completed, the reaction mixture was stirred at room temperature for 30 minutes and, since no crystals appeared, for an additional 30 minutes in an ice bath, a white crystalline precipitate then being formed. The crystals were recrystallized from water to yield 64 parts of 3 (p-iodophenyl) -1,1-bis (Z-hydroxyethyl) urea which melted at 112.5 to 113 C. This is 73% of the theoretical yield.

AinaL-Calcd for C11H15INO3: C, 37.75%; H, 4.32%. Found: C, 37.63%; H, 4.42%.

EXAMPLE IV 3- (m-fluorophenyl) -1,1 -bz's (2 -hydroryethyl) area To a stirred solution of 18 parts of diethanolamine in 51.5 parts of dry dioxane was added dropwise a solution of 21.5 parts of m-fluorophenyl isocyanate in 67 parts of dry dioxane, while'the temperature of the reaction mixture was maintained at 20-30 C. with a cooling bath. After the addition of the isocyanate was completed, 220 parts of dry benzene was added. The white crystals which separated were recovered by filtration and dried in a vacuum (30 mm.) oven at room temperature. The 3-(m-fluorophenyl) -1,1-bis-(2-hydroxyethyl) urea thus obtained melted at 84 to 85 C. and amounted to 29 parts. This was 76.5% of the theoretical yield.

Anal.-Calcd for C11H15FN203: C, 54.55%; H,

6.24%. Found: C, 54.43%; H, 6.54%.

EXAMPLE V 3 (2,4,6 trichlorophenyl) 1,1 bis 2 hydroscyethyl) urea To a stirred solution of 25.6 parts of diethanolamine in 103 parts of dry dioxane was added dropwise a solution of 48.5 parts of 2,4,6-trichlorophenyl isocyanate in 103 parts of dry dioxane. Sufficient heat was liberated to raise the temperature nearly to reflux. After the addition of the isocyanate was completed and the reaction mixture had cooled to room temperature, 440 parts of dry benzene was added. The crystals which formed were removed by filtration and dried in a vacuum (30 mm.) oven at 50 C. The 3-(2,4,6-trichlorophenyl) -1,1-bis (2-hydroxyethyl) urea thus obtained melted at 121-122 C. and amounted to 60 parts. This was 82.5% of the theoretical yield.

AnaZ.-Calcd for Cpl-11301351203: C, 40.45%;

H, 4.00%. Found: C, 40.12%; H, 4.27%.

EXAMPLE v1 3 (4 chloro 1 naphthyl) 1,1 bmz by droozyethyl) urea To a stirred solution of 21.4 parts of diethanolamine in 206 parts of dry dioxane was added dropwise a solution of 37.5 parts of 4-chloro-1- naphthyl isocyanate in 51.5 parts of dry dioxane. The reaction mixture warmed during the addition of the isocyanate. When the addition of the isocyanate was completed, 440 parts of dry benzene were added to precipitate the product. The resulting white crystalline precipitate was removed by filtration and dried in a vacuum (30 mm.) oven at 50 C. The 3-(4-chloro-1 naphthyl) -1,1-bis(2-hydroxyethyl) urea thus ob- A-l i' 51ft partsi; This is 96-55%? of" thetheoretical To a stirred suspension of '70 parts-.-of=.methyl glucamine in 206 parts of dry dioxane was added dropwise a solution of 50Eparts of p-chlorophenyl isocyanate in 51.5pa'rts ofi'dry dioxane. Heat was liberated slowly duringEthis addition. When the .solutiorr. had. warmed. to; near reflux, all A of triemethyl'guiatmhe fiaetdissmved; nourzfiundiiedfdrty, 405 parts'dfdififb'er'izerle wasadheu tdltlie' reaction-mixture, andia separated'. on; Tong, stafidingexpo creiw the air}.,a" peruse of this syrup crystallizedll IfVsi'rigT the crystalline ,material to induce. further? crystallizatioff th. rlem'aiiidei" of: the product was. rerystallized. ffornldioxafiesas meimonbnyaratei of 3;- (p chlbrcpfiefiyn' 1. methyl) 1..- gluon.- ("2,3;4;5',e pentaiiydroxyuexyl)ure'a; me'ited at 64.65 C. and amounted to 82' parts. The yield was 72% of the theoretical.

AnaL-Calcd fon'G'mHE-aGlNwv: C, 46.00%; H, 6.35%. Found: C, 46i14%;;H, 6.65%.

Thisinvention is broadly applicable to N ,N,N'-

trisubstituted urea's" ofie' monoval ent riaicge'riqaryr-ra-dical riuclarly'jattaichedto'one of the urea nitrogens: the other urea: nitrogen, if; beiiigdi'sub'stituted" and joined to two hy= 'qi'exyamyiradicals; particularlystraight-chain nyuroxyalkyiradfcmsortw -to sixc'arbon atoms; or-wdde-orthese liyarcxyaikylradicals and one alkyl radical, preferabl'yal'ower alkyl radical" of amateur-carbonarenas: Theha'rlbgenoarylradicals can be anycri'tire mcncvaiene halogenated aromatic hydrocarbon radicals, but, because of lower cost; in ger'ierar; of the preparative raw materials, those ureas having halogenated aryl radicals containing one" to two nuclei, such as phenyl, tolyl, xylyl, xenyl, naphthyl, methylnaphthyl, and the like are preferred. Particularly preferred ureas of the invention have halogenophenyl radicals containing from one to three halogen substituents on the aryl ring. The halogens can be fluorine, chlorine, bromine or iodine as shown by the examples.

The hydroxyalkyl radicals can be any of the monohydroxy and polyhydroxyalkyl radicals, but, because of more ready availability and satisfactory reactivity with the halogenoaryl isocyanates, RNCO, of the secondary aliphatic amines, RR"NH, from which the new ureas are prepared, straight-chain hydroxylated alkyl radicals having from two to six carbon atoms and up to five hydroxyl groups are preferred.

Examples of these include hydroxyethyl, -CH2CH2OH; hydroxypropyl,

dihydroxyisopropyl,

" -c;e+cm d:ei

t'et'ral'iydro'xyper'ity.l', CI-Iz:-(CHOH)E.CHOH pentahy'droxyliexyl --CH5.( CHOHX; CHzOHiL Especially preferred? among; these; hyuroxyaixyi radicals"..,bie'causel of availability; are the hydrcxyietii lfi and; ritahydrcxyhexyl' radicals.

'iiiealliiyl'i radicals. attached in comf'uiiction witfi afl hydrcxyalkyrradicar"to" the same disub stituted'ur'ea nitrcgenatom;arebacame octets-er water solubility characteristics, preferably of from one. to: four carbon atoms, for example methyl, ethyl;propyfandibutyli lowing examples dfcompomrdso'ftne' invention are given as further illustration. These" courpounds can, of course, readily be prepared by methods similar tosth'oseset-out in detail in the numbered examples. above:

The new ureas of this invention are, for the most part, White crystalline and practically odorless solids, insoluble in benzene and ethylene dichloride, but soluble in acetone, dioxane, ethyl acetate and ethanol. They are also appreciably soluble in water, differing markedly in this respect from the corresponding 3-halogenoaryl-1,1- dialkyl ureas, which are water insoluble and limited thereby in their usefulness for certain applications.

The new ureas are useful in herbicidal compositions and, moreover, are valuable chemical intermediates. They may be sulfonated, esterified, or converted to the N-methylol derivatives which are modifiers for urea-formaldehyde derivatives.

As many apparently widely different embodiments of this invention may be made without departing from the spirit and scope thereof, it is to be understood that this invention is not limited to the specific embodiments thereof except as defined in the appended claims.

We claim:

1. A tri-substituted urea having a hydrogen atom directly attached to a urea nitrogen atom which is bonded to a nuclear carbon of a halogenoaryl radical, said urea being represented by the formula wherein R is a halogenoaryl radical containing 1 to 2 nuclei, R is a hydroxyalkyl radical of 2 to 6 carbon atoms containing not more than 5 hydroxyl groups with a chain of a least 2 carbon atoms separating the urea nitrogen from the nearest hydroxyl group and R" is a radical selected from the class consisting of alkyl radicals of 1 to 4 carbon atoms and hydroxyalkyl radicals of 2 to 6 carbon atoms containing not more than 5 hydroxyl groups with a chain of at least 2 carbon atoms separating the urea nitrogen from the nearest hydroxyl group.

2. A tri-substituted urea having a hydrogen atom directly attached to a urea nitrogen atom which is bonded to a nuclear carbon of a halogenoaryl radical, said urea being represented by the formula wherein R is a halogencaryl radical containing 1 to 2 nuclei and R and R" are hydroxyalkyl radicals of 2 to 6 carbon atoms containing not more than 5 hydroxyl groups with a chain oi at least 2 carbon atoms separating the urea nitrogen from the nearest hydroxyl group.

3. A tri-substituted urea having a hydrogen atom directly attached to a urea nitrogen atom which is bonded to a nuclear carbon of a halogenoaryl radical, said urea being represented by the formula wherein R is a halogenoaryl radical containing 1 to 2 nuclei, R is a hydroxyalkyl radical of2 to 6 carbon atoms containing not more than 5 hydroxyl groups with a chain of at least 2 carbon atoms separating the urea nitrogen from the nearest hydroxyl group and R" is an alkyl radical of 1 to 4 carbon atoms.

4. A tri-substituted urea having a hydrogen atom directly attached to a, urea nitrogen atom which is bonded to a nuclear carbon of a halogenophenyl radical, said urea being represented by the formula wherein R is a halogenophenyl radical and R and R" are hydhroxyalkyl radicals of 2 to 6 carbon atoms containing not more than 5 hydroxyl groups with a chain of at least 2 carbon atoms separating the urea nitrogen from the nearest hydroxyl group.

5. A tri-substituted urea having a hydrogen atom directly attached to a urea nitrogen atom which is bonded to a nuclear carbon of a halogenophenyl radical, said urea being represented by the formula No references cited. 

1. A TRI-SUBSTITUTED UREA HAVING A HYDROGEN ATOM DIRECTLY ATTACHED TO A UREA NITROGEN ATOM WHICH IS BONDED TO A NUCLEAR CARBON OF A HALOGENOARYL RADICAL, SAID UREA BEING REPRESENTED BY THE FORMULA 